The cytoprotective peptide humanin is induced and neutralizes Bax after pro-apoptotic stress in the rat testis.
The cytoprotective peptide humanin is induced and neutralizes Bax after pro-apoptotic stress in the rat testis.
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DOI：
10.1111/j.2047-2927.2013.00091.x
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发表时间：
2013-07
期刊：
影响因子：
4.5
通讯作者：
Wang C
中科院分区：
文献类型：
--
作者：
Jia Y;Lue YH;Swerdloff R;Lee KW;Cobb LJ;Cohen P;Wang C
我们以前已经证明，来自于睾丸的细胞保护肽humanin（HN），当给药intratesticulated大鼠，拯救生殖细胞凋亡继发于睾丸应激的激素剥夺促性腺激素释放激素拮抗剂（GnRH-A）。为了解释HN在改善GnRH-A诱导的生殖细胞凋亡中的作用的细胞机制，成年雄性大鼠接受以下治疗5天：1）每天睾丸内（IT）注射盐水（对照）; 2）在第1天单次皮下注射GnRH-A，每天IT注射盐水; 3）每天IT注射合成人胰岛素（HN）; 4）第1天注射GnRH-A，每天IT注射HN（GnRH-A+HN）。HN单独对生殖细胞凋亡无影响。GnRH-A增加睾丸线粒体组分中的生殖细胞凋亡和BAX。合成HN减少由GnRH-A和BAX诱导的线粒体中的生殖细胞凋亡。我们推测合成HN对GnRH-A诱导的生殖细胞凋亡的细胞保护作用是通过减弱p38 MAPK活性和增加STAT 3磷酸化介导的。用大鼠HN特异性抗体研究了合成HN对睾丸内源性HN表达的影响。GnRH-A治疗增加，但伴随治疗与合成HN降低内源性大鼠HN表达在睾丸细胞溶质和线粒体组分。免疫共沉淀实验表明，增加大鼠HN与BAX在细胞溶质睾丸馏分后GnRH-A治疗物理。免疫荧光双标证实GnRH-A处理后BAX和大鼠HN共定位于睾丸间质细胞和精母细胞的胞浆中。我们的结论是，外源性管理的合成HN的细胞保护作用介导的内源性大鼠HN与BAX在细胞质中的相互作用，防止BAX进入线粒体，以管理在大鼠睾丸促凋亡应激过程中生殖细胞的生存或死亡的命运。
We have previously demonstrated that the mitochondria-derived cytoprotective peptide humanin (HN), when administered intratesticularly to rats, rescues germ cells from apoptosis secondary to testicular stress of hormonal deprivation induced by gonadotropin-releasing hormone antagonist (GnRH-A). To decipher the cellular mechanisms of HN action in the amelioration of GnRH-A induced germ cell apoptosis, adult male rats received the following treatments for 5 days: 1) daily intratesticular (IT) injections with saline (control); 2) a single subcutaneous injection of GnRH-A on day 1 and daily IT injection of saline; 3) daily IT injection of synthetic humanin (HN); and 4) GnRH-A injection on day 1 and daily IT injection of HN (GnRH-A+HN). HN alone had no effect on germ cell apoptosis. GnRH-A increased germ cell apoptosis and BAX in the testicular mitochondrial fractions. Synthetic HN decreased germ cell apoptosis induced by GnRH-A and BAX in the mitochondria. We deduced that the cytoprotective action of synthetic HN on GnRH-A induced germ cell apoptosis was mediated by attenuating p38 MAPK activity and increasing STAT3 phosphorylation. The effect of synthetic HN on the expression of endogenous rat HN in the testis was studied using rat HN specific antibody. GnRH-A treatment increased but concomitant treatment with synthetic HN reduced endogenous rat HN expression in both cytosolic and mitochondrial fractions in testis. Co-immunoprecipitation experiments demonstrated the increased rat HN was physically associated with BAX in the cytosolic testicular fractions after GnRH-A treatment. Double-immunofluorescence staining confirmed the co-localization of BAX and rat HN in the cytoplasm of Leydig cells and spermatocytes after GnRH-A treatment. We conclude that the cytoprotective effect of exogenously administered synthetic HN is mediated by interactions of endogenous rat HN with BAX in the cytoplasm preventing the entry of BAX to the mitochondria to govern the fate of germ cell survival or death during pro-apoptotic stress to the testis in rats.
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影响因子：
4.8
作者：
Hikim, APS;Lue, YH;Swerdloff, RS
通讯作者：
Swerdloff, RS
DOI：
10.1073/pnas.94.8.3668
发表时间：
1997-04-15
影响因子：
11.1
作者：
Hsu, YT;Wolter, KG;Youle, RJ
通讯作者：
Youle, RJ
影响因子：
11
作者：
Chiba, T.;Yamada, M.;Aiso, S.
通讯作者：
Aiso, S.
影响因子：
3.3
作者：
Hashimoto, Yuichi;Kurita, Megumi;Matsuoka, Masaaki
通讯作者：
Matsuoka, Masaaki
影响因子：
64.8
作者：
Guo, B;Zhai, DY;Reed, JC
通讯作者：
Reed, JC